Organic compounds

ABSTRACT

The invention relates to organic compounds having the ability to reduce or suppress the onset of skin irritation induced by extraneous cause selected from the group of 2-heptylcyclopentanone, 2-ethoxynaphthalene; 2-methoxynaphthalene; 1-methoxy-4-(prop-1-enyl)benzene; 1-(cyclopropylmethyl)-4-methoxybenzene; 
     
       
         
         
             
             
         
       
         
         
           
             wherein X, Y, and R 1  to R 11  have the same meaning as given in the description. 
           
         
       
    
     Furthermore the invention refers to compositions for topical application to the skin comprising them. It further relates to a method of reducing or suppressing the formation of skin irritation.

This is a divisional patent application of U.S. Ser. No. 13/006,791filed on 14 Jan. 2011, which in turn, is a divisional patent applicationof U.S. Ser. No. 12/066,518 filed 17 Oct. 2008, which in turn is basedon PCT/CH2006/000481 filed 8 Sep. 2006, which application claimspriority to GB 0518558.2 filed 12 Sep. 2005. The applicant claims allavailable priority benefits afforded by these applications, andincorporates by reference into the present application the entirely oftheir disclosures.

The present invention relates to organic compounds having the ability toreduce or suppress the formation of skin irritation induced byextraneous causes, and to compositions comprising them for topicalapplication to the skin. It further relates to a method of reducing orsuppressing the onset of skin irritation by extraneous causes.

The human skin is constantly exposed to environmental stresses, such asheat and cold, air pollution, exceptionally dry air or exaggerated UVirradiation. A further form of stress can come from the application ofcosmetic products or personal wash products. For example, certain soapacids and some surfactants, in particular anionic and cationicsurfactants, are known to stress the skin. Antiperspirant salts, such asaluminum salts and zirconium salts contained in antiperspirant products,retinol and derivatives thereof contained in anti-aging products,α-hydroxy acids such as glycolic acid or lactic acid contained inanti-wrinkle products are also known to stress the skin.

It is known from the art that prostaglandins are mediators being formedupon a wide variety of different forms of external stress applied to thehuman skin, which may become apparent in redness of the skin,particularly on normal, healthy skin. Thus there is a need for additivesin topical application compositions, such as cosmetic products andpersonal wash products, which suppress or reduce the formation ofprostaglandins, in particular prostaglandin E₂ (PGE₂).

Surprisingly the inventors have found that certain classes of chemicalcompounds, most of which are known as fragrance ingredients, have theability to reduce or suppress the formation of prostaglandins in skincells.

Thus the present invention refers in one aspect to the use of a compoundfor the preparation of topical skin care compositions for reduction ofskin irritation, wherein the compound is selected from the listconsisting of

-   -   (a) compounds of the formula

-   -   -   wherein        -   R is hydrogen or isopropyl;        -   R¹ is methyl or ethyl; and R² is C₁-C₆ alkyl or C₂-C₆            alkenyl; or        -   R¹ and R² together with the carbon atom to which they are            attached form a C₅ or C₆ cycloalkyl ring; and        -   the dotted line together with the carbon carbon bond            represents a single bond or a double bond;

    -   (b) compounds of the formula

-   -   -   wherein Y is a C₄-C₇ hydrocarbon residue, e.g. cyclohexyl,            n-hexyl, n-pentyl, iso-butyl, cis-3-hexen-1-yl, phenethyl,            and 1-methyl-hex-3-en-1-yl;

    -   (c) compounds of the formula

-   -   -   wherein        -   R⁴ is methyl or ethyl and        -   I) R³ is hydrogen and R⁵ is —CH₂—O—R⁶, wherein R⁶ is methyl            or isopropyl; or        -   II) R³ is —C(O)—R⁷, wherein R⁷ is benzyl, and R⁵ is            —CH₂—CH═CH₂,

    -   (d) compounds of the formula

-   -   -   wherein        -   R⁸ is methyl, C₃-C₄ alkyl, C₃-C₄ alkenyl, —(CH₂)₂-Ph, or            —CH═CH-Ph;        -   X is —CH═CH—CH₂— or —(CH₂)_(n)—, wherein n is 1 or 2; and        -   R⁹ is isobutyl or phenylethyl;

    -   (e) compounds of the formula

-   -   -   wherein        -   R¹⁰ is hydrogen or methyl; and        -   R¹¹ is a C₃-C₄ alkyl, e.g. isopropyl, isobutyl or            tert-butyl,

    -   and

    -   (f) 2-heptylcyclopentanone, 2-ethoxynaphthalene,        2-methoxynaphthalene, 1-methoxy-4-(prop-1-enyl)benzene and        1-(cyclopropylmethyl)-4-methoxybenzene.

Particularly preferred is the use of compounds selected from the listconsisting of 2-cyclohexylidene-2-phenylacetonitrile,2-cyclopentylidene-2-phenylacetonitrile,3-ethyl-2-phenylpent-2-enenitrile, 2-ethoxy-4-(isopropoxymethyl)phenol,2-ethoxy-4-(methoxymethyl)phenol, phenethyl cinnamate,4-allyl-2-methoxyphenyl 2-phenylacetate, n-hexyl salicylate,cis-3-hexen-1-yl salicylate, cyclohexylsalicylate (=cyclohexyl2-hydroxybenzoate), amylsalicylate (=pentyl 2-hydroxybenzoate),isobutylsalicylate (=isobutyl 2-hydroxybenzoate), phenylethyl benzoate,benzyl 2-methylbut-2-enoate, 2-methyl-3-(4-isopropylphenyl)propanal,isobutyl benzoate, cinnamyl cinnamate, phenethyl salicylate,2-methyl-3-(4-(2-methylpropyl)phenyl)propanal, 2-heptylcyclopentanone,2-ethoxynaphthalene, 2-methoxynaphthalene,1-methoxy-4-(prop-1-enyl)benzene, phenethyl pivalate,1-(cyclopropylmethyl)-4-methoxybenzene, cinnamyl acetate,3-(4-tert-butylphenyl)propanal, phenethyl 2-methylbutanoate, andphenethyl isobutyrate.

The availability of a greater number of compounds, which in addition totheir odoriferous properties, have the ability to reduce or suppress theformation of skin irritation provides the perfumer with an adequateamount of molecules some of which posses quite varied odor notes, tocreate hedonically attractive fragrance compositions while providingreduction of skin irritation and/or redness reduction activity to theskin to which it is applied. In particular, the use of multiple perfumeingredients permits the design of hedonically attractive fragranceaccords.

The actives for reducing skin irritation as hereinabove described may becombined with all known odorant molecules selected from the extensiverange of natural products and synthetic molecules currently available,such as essential oils, alcohols, aldehydes and ketones, ethers andacetals, esters and lactones, macrocycles and heterocycles, and/or inadmixture with one or more ingredients or excipients conventionally usedin conjunction with odorants in fragrance compositions, for example,carrier materials, and other auxiliary agents commonly used in the art.Such ingredients are, for example, described in “Perfume and FlavorMaterials of Natural Origin”, S. Arctander, Ed., Elizabeth, N.J., 1960;“Perfume and Flavor Chemicals”, S. Arctander, Ed., Vol. I & II, AlluredPublishing Corporation, Carol Stream, USA, 1994; and “Internationalcosmetic ingredient dictionary” 6^(th) ed., The Cosmetic, Toiletry andFragrance Association, Inc., Washington, 1995.

While lower concentrations of the active compound show an effect in acell culture system, as can be seen from the examples, higherconcentrations in personal care products are necessary to allow for aneffective concentration on the human skin even if, for example part ofthe product may be removed by abrasion of clothes or may be diluted bysweat. Furthermore, the healthy skin acts as a barrier which limits thepenetration of the active compounds. Generally, the concentration ofactive compound needed for efficaciousness on skin is from about 50 to100 times higher than that needed in in-vitro tests. The usual perfumeconcentration in a topical cosmetic product is about 0.3 to 2% byweight. In general, the amount of actives applied is in the range offrom 0.2 to 2% by weight, based on the end-product applied to the skin,the amounts applied usually being in the range of from 0.3 to 1% byweight.

Thus the present invention refers in a further aspect to fragrancecompositions comprising at least 30 weight % based on the totalfragrance composition of at least two actives for reducing skinirritation as hereinabove described.

Whereas some active compounds may be used in relatively high amounts ina fragrance composition others which are known to be very powerfulodorants, such as Neroline™ and Propyl Diantilis, may be used only insmaller amounts in order to avoid negatively effecting the overallhedonic impression of the fragrance composition. In general, as theoverall proportion of the active compound in the fragrance compositionrises, so should the number of active compounds used. For example, afragrance composition comprising more than 40 weight % of activecompounds should preferably contain at least 4 different actives, afragrance composition comprising more than 50 weight % of activecompounds should preferably contain at least 5 different actives, and afragrance compositions comprising more than 60 weight % of activecompounds should preferably contain at least 6 different actives. Thus,in a further aspect the present invention refers to fragrancecompositions comprising at least 30 weight % of at least three, four orfive actives for reducing skin irritation. Optionally the fragrancecomposition according to the present invention comprises at least two,three or four actives of which are selected from a different group ofcompounds, namely group (a), (b), (c), (d), (e), and (f) as hereinabovedescribed.

From a hedonic point of view the actives are selected from two differentgroup of compounds. In particular embodiments are fragrance compositionscomprising a compound of formula (a) and a compound of formula (b), andfragrance compositions comprising a compound of formula (c) and acompound of formula (d) or (d′). As can be seen from the examples,fragrance compositions which are both hedonically attractive and whichhave irritation reducing properties may be prepared, for example, if thecomposition comprises at least four active compounds, each of which isselected from a different group of compounds.

In an other embodiment the invention is directed to fragrancecompositions comprising

(a) at least one compound of the formula

-   -   wherein    -   R is hydrogen or isopropyl;    -   R¹ is methyl or ethyl; and R² is C₁-C₆ alkyl or C₂-C₆ alkenyl;        or    -   R¹ and R² together with the carbon atom to which they are        attached form a C₅ or C₆ cycloalkyl ring; and    -   the dotted line together with the carbon carbon bond represents        a single bond or a double bond;        (b) at least one compound of the formula

-   -   wherein Y is a C₄-C₇ hydrocarbon residue, e.g. cyclohexyl,        n-hexyl, n-pentyl, iso-butyl, cis-3-hexen-1-yl, phenethyl, and        1-methyl-hex-3-en-1-yl;        (c) at least one compound of the formula

-   -   wherein    -   R⁴ is methyl or ethyl and    -   I) R³ is hydrogen and R⁵ is —CH₂—O—R⁶, wherein R⁶ is methyl or        isopropyl; or    -   II) R³ is —C(O)—R⁷, wherein R⁷ is benzyl, and R⁵ is —CH₂—CH═CH₂;        and        (d) at least one compound of the formula

-   -   wherein    -   R⁸ is methyl, C₃-C₄ alkyl, C₃-C₄ alkenyl, —(CH₂)₂-Ph, or        —CH═CH-Ph;    -   X is —CH═CH—CH₂— or —(CH₂)_(n)—, wherein n is 1 or 2; and    -   R⁹ is isobutyl or phenylethyl.

Furthermore, the present invention refers to topical skin carecompositions, such as cosmetic products and personal wash products,comprising about 0.2 to about 3 weight %, preferably about 0.5 to about2.5 weight % of a fragrance composition, the fragrance compositioncontaining at least 30 weight % of at least two actives selected fromthe group (a), (b), (c), (d), (e), and (f) as hereinabove described,with the proviso that the topical skin care composition comprises atleast 0.2 weight % of actives based on the total amount of the skincomposition. In particular embodiments are topical skin carecompositions wherein the fragrance composition containing a compound offormula (a) and a compound of formula (b), and topical skin carecomposition wherein the fragrance composition containing a compound offormula (c) and a compound of formula (d) or (d′).

In another aspect the present invention is directed to a method ofreducing the onset of skin irritation by applying to the skin aneffective amount of a topical skin care composition comprising afragrance composition, the fragrance composition containing at least 30weight % based on the total fragrance composition of at least twoactives as defined hereinabove, with the proviso that the topical skincare composition comprises at least 0.2 weight % of actives based on thetotal amount of the skin composition.

An “effective amount” is generally achieved if about 5-50 mg/cm² skin orabout 0.05 to about 0.5 mm thick film of the topical skin product isapplied to the skin.

As used within the meaning of the present invention the expression “atleast 30 weight %” includes fragrance compositions comprising at least35, 40 or even 45 or 50 weight % of at least two actives as definedhereinabove. The term “actives” and “active compounds” as used withinthe meaning of the present invention refers to all compounds selectedfrom the list of compounds of formula (a), (b), (c), (d), (d′), (e) and2-heptylcyclopentanone, 2-ethoxynaphthalene, 2-methoxynaphthalene,1-methoxy-4-(prop-1-enyl)benzene and1-(cyclopropylmethyl)-4-methoxybenzene.

Topical skin care compositions of the present invention may be dividedinto two classes of products, that is, cosmetic products and topicalwashing products, and may include but is not limited to antiperspirants,deodorants, day and night creams, shaving products, hand creams, bodylotions, hair shampoo and conditioners, lipsticks, after-sun products,hand lotions, foundation creams, moisturizing creams, skin food, skintonics, skin lightening products and overnight facial masks. Thecompositions may be in any form. These forms may include lotions,creams, sticks, roll-on formulations, mousses, aerosol sprays,pad-applied formulations, powders, tonics, and emulsions (oil-in-water,water-in-oil, or mixed emulsion systems).

The invention is now further described with reference to the followingnon-limiting examples. All of the amounts are given as percentageamounts by weight, unless otherwise indicated.

EXAMPLE 1: SCREENING FOR COMPOUNDS PROTECTING KERATINOCYTES AGAINSTIRRITATING AGENTS

Normal human epidermal keratinocytes (NHEK) were obtained from skinbiopsies and maintained as described by Rheinwald and Green (cell,6:331-344, 1975) in keratinocyte growth medium supplemented with 10%heat inactivated fetal calf serum at a humidity of 98% in a 5% carbondioxide atmosphere. A confluent culture was trypsinated and adjusted toa density of 5×10⁴ cells/ml. The cells were then seeded in the samemedium but with only 1% fetal calf serum in 24 well plates andcultivated for a period of 48 h. A model irritating agent was thenapplied to the cells by adding calcimycin to a final level of 2.5 μM.The individual compounds, as listed below, dissolved in DMSO were addedsimultaneously. The final concentration of the compounds was 50 μM or 10μM, the final DMSO concentration was adjusted to 1% (v/v). Paralleltreatments received no calcimycin (non-irritated control) or calcimycinwithout compounds according to the present invention (irritatedcontrol). The DMSO concentration was adjusted to 1% in all these controltreatments. After 24 h incubation, the supernatant of the cells washarvested, diluted 1:1 and added to an enzyme linked immunoassay kit forthe specific detection of prostaglandin E₂ as a marker of cellularirritation (Product #404110, Neogen corporation, Lexington Ky. 40505,USA). The prostaglandin levels in treated cell cultures were compared tothe irritated and non-irritated control cultures in order to determinethe relative inhibition of PGE₂ formation. Results for the individualcompounds are listed below.

relative inhibition in % of PGE₂ formation in keratinocyte cultures atCompound 50 μM 10 μM PEONILE ® (2-cyclohexylidene-2- 93.3 92.4phenylacetonitrile) PROPYL DIANTILIS 90.9 95.1(2-Ethoxy-4-(isopropoxymethyl)phenol) METHYL DIANTILIS ® n.d. 88.2(2-Ethoxy-4-(methoxymethyl)phenol) Phenethyl cinnamate 91.7 93.6 EUGENYLPHENYL ACETATE 96.6 99 (Phenyl 2-(4-allyl-2-methoxyphenyl)acetate)n-Hexyl salicylate 82.9 91.6 cis-3-Hexen-1-yl salicylate 94.8 81.4Cyclohexyl salicylate 97.4 76.6 Amyl salicylate 89.8 73.5 Isobutylsalicylate 69.1 73.1 Phenethyl benzoate 92.4 56.9 TIGLATE BENZYLE(benzyl 2-methylbut-2-enoate) 72.4 50.2 CYCLAMEN ALDEHYDE ™ 82.0 32(2-Methyl-3-(4-isopropylphenyl)propanal) Isobutyl benzoate 52.5 n.d.Cinnamyl cinnamate 64.0 n.d. Phenethyl salicylate 50.9 n.d. SILVIAL ®62.7 n.d. (2-Methyl-3-(4-(2-methylpropyl)phenyl)propanal) ALISMONE ™(2-heptylcyclopentanone) 92.4 47 NEROLINE ™ CRIST (2-ethoxynaphthalene)83 50.2 YARA YARA ™ (2-methoxynaphthalene) 78 46 ANETHOLE(1-methoxy-4-(prop-1-enyl)benzene) 51 n.d. CENTIFOLYL ™ (phenethylpivalate) 39 n.d. TOSCANOL ® (1-(cyclopropylmethyl)-4- 56.7 n.d.methoxybenzene) Cinnamyl acetate 47.8 n.d. BOURGEONAL ™(3-(4-tert-butylphenyl)propanal) 65.0 n.d. ANATOLYL ™ (phenethyl2-methylbutanoate) 50.5 n.d. Phenethyl isobutyrate 44.8 n.d.2-Cyclopentylidene-2-phenylacetonitrile 80.8 71.13-Ethyl-2-phenylpent-2-enenitrile 73.2 63.9 n.d. = not determined

Similar results as listed above were obtained by irritation of the cellseither by UVB irradiation or exposure to the skin cells to irritatingcationic surfactant benzalkonium chloride.

EXAMPLE 2: FRAGRANCE COMPOSITIONS WITH THE PROPERTIES TO REDUCE ORSUPPRESS THE FORMATION OF SKIN IRRITATION 2.1 Floral FragranceComposition No. 1

parts by weight 1/100 Peonile ® 18.90 Alismone ™ 5.30 Cyclohexylsalicylate 12.10 Silvial ® 6.80 Toscanol ® 0.15 Floral fragrance base56.75

2.2 Floral Fragrance Composition No. 2

parts by weight 1/100 PEONILE ® 1.00 PROPYL DIANTILIS 0.01 Phenethylcinnamate 0.20 Hexyl salicylate 40.00 cis-3-Hexen-1-yl salicylate 1.00Amyl salicylate 3.00 NEROLINE ™ 0.10 Floral fragrance base 54.69

2.3 Floral-Fruity Fragrance Composition No. 3

parts by weight 1/900 Citronellyl acetate 10 Cyclamen aldehyde ™* 3Ambrettolide (oxacycloheptadec-10-en-2-one) 40 Ambrofix (CAS No.6790-58-5) 10% in dipropyleneglycol 8 Bourgeonal ™* 30 Centifolyl ™* 45Dihydromyrcenol (2,6-dimethyloct-7-en-2-ol) 8 Ethyllinalool(3,7-dimethyl-1,6-nonadien-3-ol) 45 Florol ®(tetrahydro-2-isobutyl-4-methyl-2H-pyran-4-ol) 25 Galaxolide ®(1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta- 12gamma-2-benzopyran) 50% dissolved in isopropylmyristate Hedione ®(methyl 2-(3-oxo-2-pentylcyclopentyl)acetate) 250 Cis-3-hexenol 10% indipropyleneglycol 3 Phenethyl isobutyrate* 25 Ethyl-2-methyl-butyrate10% in dipropyleneglycol 3 Neroline ™* 10% in dipropyleneglycol 2 Orangeessence brazil 15 Pomarose (5,6,7-trimethylocta-2,5-dien-4-one) 10% indipropyleneglycol 3 Prunella ® subst (compounded perfumery base fromFirmenich) 3 Cyclohexyl salicylate* 75 cis-3-Hexen-1-yl salicylate* 100n-Hexyl salicylate* 20 Phenylethyl salicylate* 80 Silvial ®* 45Tropional (2-methyl-3-(3,4-methylenedioxyphenyl)propanal) 40 Velvione ®(5-cyclohexadecen-1-one) 10 All ingredients marked with an * are activecompounds having the ability to reduce or suppress the formation of skinirritation, as defined according to the present invention. The fragrancecomposition No. 3 comprises 47 weight % of actives.

2.4 Floral-Fruity Fragrance Composition No. 4

parts by weight 1/900 Benzyl-acetate 14 2-Phenylethanol 200 Cyclamenaldehyde ™* 3 Bourgeonal ™* 3 Centifolyl ™* 80 Phenethyl-cinnamate* 25Citronellol 25 1-(1,1-Dimethoxypropan-2-yl)benzene 8 Dione(2-[2-(3,3,5-trimethylcyclohexyl)-1-ethanone]cyclopentanone) 3 10% indipropyleneglycol Dipropyleneglycol 128 Gardenol (alpha-Methylbenzylacetate) 5 Georgywood (1-(1,2,3,4,5,6,7,8-octahydro-1,1,7,8-tetramethyl-2 naphthalen-7-yl)ethanone) Geraniol 30 Hedione ® 70 Heliotropine 4Indolene (8-(1H-indol-2-yl)-8-(1H-indol-3-yl)-2,6-dimethyloctan-2-ol) 1Isoraldeine 70 (mixture of 4/1-(2,6,6-trimethyl-2-cyclohexen-1-yl)- 253-methyl-3-buten-2-one) Methyl diantilise ®* 25 Neroline ™* 1 Patchouliessential oil rectified (origin: Indonesia) 2 Peach pure(5-heptyl-dihydrofuran-2(3H)-one) 10 Pharaone(2-Cyclohexyl-1,6-heptadien-3-one) 1% in dipropyleneglycol 8 Pomarose10% in dipropyleneglycol 3 Rose oxide 7 Cyclohexyl salicylate* 45cis-3-Hexenyl salicylate* 55 n-Hexyl salicylate* 20 Phenethylsalicylate* 80 Vanillin 5 Viridine (phenylacetaldehyde dimethyl acetal)3 Ylang Ylang essential oil 10 All ingredients marked with an * areactive compounds having the ability to reduce or suppress the formationof skin irritation, as defined according to the present invention. Thefragrance composition No. 3 comprises 37.4 weight % of actives.

2.5 Fresh, Woody Floral Fragrance Composition No. 5

parts by weight 1/1000 Azurone 10% in triethyl citrate 4(7-(3-Methylbutyl)-2H-1,5-benzodioxepin-3(4H)-one) Ethyl vanilline 10%in DPG 4 Evernyl ™ (methyl 2,4-dihydroxy-3,6- 2 dimethylbenzoate)Fixolide 55 (1-(3,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethanone) Florhydral ® (3-(3-isopropylphenyl)butanal) 5 Iso Esuper ™ 250 (1-(2,3,8,8-tetramethyl-1,2,3,4,5,6,7,8-octahydronaphthalen-2-yl)ethanone) Kephalis 30(4-(1-ethoxyvinyl)-3,3,5,5-tetramethylcyclohexanone) Cyclohexal 80Linalool (3,7-dimethylocta-1,6-dien-3-ol) 40 Patchouli essential oil 10Peonil ®* 100 Diethyl phthalate 60 Radjanol ™(2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten- 50 1-yl)-2-buten-1-ol)Phenethyl salicylate* 100 cis-3-Hexen-1-yl salicylate* 55 n-Hexylsalicylate* 55 Serenolide ™ 60(2-(1-(3,3-dimethylcyclohexyl)ethoxy)-2-methylpropylcyclopropanecarboxylate) Velvione ® 40 All ingredients marked with an *are active compounds having the ability to reduce or suppress theformation of skin irritation, as defined according to the presentinvention. The fragrance composition No. 5 comprises 31 weight % ofactives.

2.6 Floral, Spicy, Green Fragrance Composition No. 6

parts by weight 1/948 Dimethyl benzyl carbinyl acetate 25 Linalyleacetate 70 Phenylethyl alcohol 75 Methyl anthranilate 3 Cosmone(3-methylcyclotetradec-5-enone) 40 Florol ®(2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol) 70 Galbanum oil 35Gardenol 15 Hedione ® 55 Indole 1% in dipropyleneglycol (DPG) 45Isoraldeine 70 80 Methyl diantilise ®* 45 Nirvanolide ™(13-methyloxacyclopentadec-10-en-2-one) 45 Peche pure 3 Peonile ®* 55EUGENYL PHENYL ACETATE* 20 Phenethyl salicylate* 100 Cis-3-Hexen-1-ylsalicylate* 100 Vertofix coeur (methyl cedryl ketone) 55 Ylang Ylangessential oil 12 All ingredients marked with an * are active compoundshaving the ability to reduce or suppress the formation of skinirritation, as defined according to the present invention. The fragrancecomposition No. 6 comprises 33.7 weight % of actives.

2.7 Floral, Rosy, Fruity Fragrance Composition No. 7

parts by weight 1/825 Benzyl-acetate 20 2-Phenylethanol 200 Phenethylbenzoate* 130 Centifolyl ®* 45 Cinnamyl cinnamate* 10 Phenyl ethylcinnamate* 52 Citronellol 45 Dihydrofarnesal ™(3,7,11-trimethyldodeca-6,10-dienal) 20 Florhydral ™(3-(3-isopropylphenyl)butanal) 3 Hedione ® 150 Phenethyl isobutyrate* 25Isoraldeine 70 45 Methyl diantilis ®* 45 Peche pure 10 Rose oxide 10Vanillin 15 All ingredients marked with an * are active compounds havingthe ability to reduce or suppress the formation of skin irritation, asdefined according to the present invention. The fragrance compositionNo. 7 comprises 37.2 weight % of actives.

EXAMPLE 3: EFFECT OF FRAGRANCE COMPOSITIONS ON KERATINOCYTE CULTURES

Keratinocytes were grown in 24 well plates and irritated with calcimycinas described in example 1. Fragrance compositions of example 2 weredissolved in DMSO and added to the cultures simultaneously. Inhibitionof PGE₂ formation was measured as described in example 1. The resultsare listed in Table 1.

TABLE 1 Relative inhibition in % of PGE₂ formation at differentconcentration of test fragrance 12.5 ppm 6.25 ppm Composition No. 1 79.042.4 Composition No. 2 82.6 85.6 Floral fragrance base 0 0

As can been seen from the FIGURES in Table 1, about 80% reduction ofPGE₂ formation was observed at 12.5 ppm if a fragrance compositionaccording to the present invention is applied, whereas using the floralfragrance base without actives, no measurable reduction of PGE₂formation was observed.

EXAMPLE 4: IRRITATION REDUCING EFFECTS OF A HYDROGEL ON RECONSTITUTEDEPIDERMIS

A hydrogel was prepared as follows:

INGREDIENT SUPPLIER INCI NAME % W/W CARBOPOL 980 Goodrich Carbomer 0.50PEMULEN TR1 Goodrich Acrylate/C10-030 0.20 Alkyl acrylate crosscopolymerLUBRAGEL CG Guardian Polyglycerylmethacrylate & 0.50 Propylene glycolUCON 75H450 Amerchol PEG/PPG-17/6 copolymer 1.00 GLYCERIN AMI Glycerin4.00 HEXYLENE GLYCOL Hexylene Glycol 2.00 DEIONISED WATER Water qsq100.00 GERMALL 115 Sutton Imidazolidinyl Urea 0.60 SODIUM HYDROXIDESodium Hydroxide 10% in water qsp pH = 5.50 CREMOPHOR RH 40 BASF PEG 40Hydrogenated Castor oil 1.00 Glycerin and water were mixed, Carbopol 980was dispersed, then Pemulen TR 1 and then the remaining ingredients wereadded.

Human reconstituted epidermis EpiDerm was purchased from Mattek(Ashland, USA). The cultures were exposed to a single Dose of 600 mJUVB, and then either 50 mg phosphate buffered saline (PBS) or 50 mg ofthe above hydrogel was added on top of the individual EpiDerm cultures.After 24 h incubation, the culture medium beneath the air exposedEpiDerm cultures was sampled and analyzed for PGE₂ as described inexample 1. All skin samples retained 100% cellular viability throughoutthe experiment. Skin samples treated with a hydrogel containing theinventive perfume composition 1 from example 2 suppressed UVB inducedPGE₂ formation.

TABLE 2 level PGE₂ per ml t-test vs t-test vs culture medium control UVBirritation Control, no UVB 8.253 1.000 UVB 600 mJ, PBS 42.143 0.0031.000 treatment UVB 600 mJ, 48.778 0.046 0.742 Hydrogel treatment UVB600 mJ, 12.135 0.384 0.001 Hydrogel containing 0.5% (w/w) fragrancecomp. No. 1

EXAMPLE 5: ANTIPERSPIRANT WITH REDUCED IRRITATION ON RECONSTITUTEDEPIDERMIS

An antiperspirant was formulated according the following formulation:

Weight % Water 67 Aluminium chlorohydrate 20 Glycerin 5 Sunflower oil 4Steareth 2 3 Steareth-20 1

The following antiperspirant compositions had been prepared:

-   -   I) antiperspirant & 1 weight % conventional perfume A    -   II) antiperspirant & 0.5 weight % conventional perfume B    -   III) antiperspirant & 0.5 weight % fragrance composition No. 1        (Ex. 2.1)    -   IV) antiperspirant & 1 weight % fragrance composition No. 1 (Ex.        2.1)

50 mg of the resulting antiperspirant I)-IV) or 50 mg of PBS as controlwas added to Mattek skin cultures as described above, and after 24 h thelevel of PGE₂ in the culture medium was determined according to theprocedure described above. The results are shown in Table 3.

TABLE 3 Level of PGE₂ in t-test vs culture medium control PBS 12.54Composition I) 35.49 0.002 Composition II) 27.66 0.011 Composition III)16.05 0.302 Composition IV) 9.48 0.368

As can be seen from the results above, antiperspirants formulated withconventional perfumes (i.e. composition I) and II)) led to significantlyenhanced PGE₂ formation indicating an irritating nature of theseproducts to the human skin, whereas upon treatment of EpiDerm withantiperspirants containing the inventive fragrance composition, nosignificantly enhanced PGE₂ levels were detected. All epidermal culturesretained 100% of the cellular viability showing that all the productsare not cytotoxic.

The invention claimed is:
 1. A topical skin care composition effectivein reducing the onset of skin irritation caused by either environmentalstresses or by stresses caused by the application of chemical compoundsto skin, comprising the following actives: (a) at least one compound ofthe formula (a):

wherein R is hydrogen or isopropyl; R¹ is methyl or ethyl; and R² isC₁-C₆ alkyl or C₂-C₆ alkenyl; or R¹ and R² together with the carbon atomto which they are attached form a C₅ or C₆ cycloalkyl ring; and thedotted line together with the carbon carbon bond represents a singlebond or a double bond; (b) at least one compound of the formula (b):

wherein Y is a residue selected from a C₄-C₇ hydrocarbon andphenylethyl; and, (c) a cosmetically acceptable carrier; wherein thetotal amount of the actives (a) and (b) is 0.2 to 2 weight % based onthe total weight of the topical skin care composition.
 2. A topical skincare composition according to claim 1, comprising as actives: (a) atleast one compound selected from 2-cyclohexylidene-2-phenylacetonitrile,2-cyclopentylidene-2-phenylacetonitrile and3-ethyl-2-phenylpent-2-enenitrile; and (b) at least one compoundselected from n-hexyl salicylate, cis-3-hexen-yl salicylate,cyclohexylsalicylate, amylsalicylate, isobutylsalicylate, and phenethylsalicylate.
 3. A topical skin care composition effective in reducing theonset of skin irritation caused by either environmental stresses or bystresses caused by the application of chemical compounds to skin,comprising as actives: (a) at least one compound of the formula

wherein R⁴ is methyl or ethyl and I) R³ is hydrogen and R⁵ is CH₂—O—R⁶,wherein R⁶ is methyl or isopropyl; or II) R³ is —C(O)—R⁷, wherein R⁷ isbenzyl, and R⁵ is —CH₂—CH═CH₂ (b) at least one compound of the formula

wherein R⁸ is methyl, C₃-C₄ alkyl, C₃-C₄ alkenyl, —(CH₂)₂-Ph, or—CH—CH-Ph; X is —CH═CH—CH₂— or —(CH₂)_(n)—, wherein n is 1 or 2; and R⁹is isobutyl or phenylethyl; (c) a cosmetically acceptable carrier;wherein the total amount of the active (a) and (b) is 0.2 to 2 weight %based on the total weight of the topical skin care composition.
 4. Atopical skin care composition according to claim 1, further comprisingas further actives at least one compound of the formula

wherein R⁴ is methyl or ethyl and I) R³ is hydrogen and R⁵ is —CH₂—O—R⁶,wherein R⁶ is methyl or isopropyl; or II) R³ is —C(O)—R⁷, wherein R⁷ isbenzyl, and R⁵ is —CH₂—CH═CH₂.
 5. A topical skin care compositionaccording to claim 1, comprising as further actives at least onecompound of the formula

wherein R⁸ is methyl, C₃-C₄ alkyl, C₃-C₄ alkenyl, —(CH₂)₂-Ph, or—CH═CH-Ph; X is —CH═CH—CH₂— or —(CH₂)_(n), wherein n is 1 or 2; and R⁹is isobutyl or phenylethyl.
 6. A topical skin care compositioncomprising about 0.5 to about 3 weight % of a fragrance compositionwhich fragrance comprises at least 30 weight % of at actives effectivein reducing the onset of skin irritation caused by either environmentalstresses or by stresses caused by the application of chemical compoundsto skin, the actives comprising: (a) at least one compound of theformula

wherein R is hydrogen or isopropyl; R¹ is methyl or ethyl; and R² isC₁-C₆ alkyl or C₂-C₆ alkenyl; or R¹ and R² together with the carbon atomto which they are attached form a C₅ or C₆ cycloalkyl ring; and thedotted line together with the carbon-carbon bond represents a singlebond or a double bond; and (b) at least one compound of the formula

wherein Y is a C₄-C₇ hydrocarbon residue.
 7. A topical skin carecomposition according to claim 1 wherein the skin composition is acosmetic product.